Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000542415 | SCV000625271 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-10-28 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000581252 | SCV000689989 | likely benign | Hereditary cancer-predisposing syndrome | 2017-06-07 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000581252 | SCV001172151 | likely benign | Hereditary cancer-predisposing syndrome | 2015-10-14 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Department of Pathology and Laboratory Medicine, |
RCV001354259 | SCV001548826 | likely benign | Carcinoma of colon | no assertion criteria provided | clinical testing | The MSH2 p.Ala499Ala variant was not identified in the literature nor was it identified in the dbSNP, the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium database (August 8, 2016), Clinvitae database, COSMIC, Mismatch Repair Genes Variant Database, MMR Gene Unclassified Variants Database, InSiGHT Colon Cancer Gene Variant Database (LOVD), Zhejiang Colon Cancer Database (LOVD), ClinVar database, GeneInsight-COGR database and UMD. The variant was identified by our laboratory as co-occurring with a pathogenic MSH6 (c.3554_3556+2delCAGGT) variant in a patient with Lynch syndrome suggesting that it may not have clinical significance. The p.Ala499Ala variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, 4 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a greater than 10% difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |